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Social Determinants of Health Extraction From Clinical Notes Across Institutions Using Large Language Models
No full textDetailed social determinants of health (SDoH) is often buried within clinical text in EHRs. Most current NLP efforts for SDoH have limitations, investigating limited factors, deriving data from a single institution, using specific patient cohorts/note types, with reduced focus on generalizability. We aim to address these issues by creating cross-institutional corpora and developing and evaluating the generalizability of classification models, including large language models (LLMs), for detecting SDoH factors using data from four institutions. Clinical notes were annotated with 21 SDoH factors at two levels: level 1 (SDoH factors only) and level 2 (SDoH factors and associated values). Compared to other models, instruction tuned LLM achieved top performance with micro-averaged F1 over 0.9 on level 1 corpora and over 0.84 on level 2 corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. Access to trained models will be made available at https://github.com/BIDS-Xu-Lab/LLMs4SDoH
SEM and Bacteriological Evidence of Laser-Activated Irrigation Compared to Ultrasonic-Activated Irrigation: A Pilot Study
No full textBackground: Pulp tissue debridement and the eradication of microorganisms from an infected root canal system before obturation is a primary focus of endodontic treatment and the best predictor for the long-term success of endodontic treatment. Objective: The purpose of this in vitro laboratory study was to evaluate pulp tissue debridement and the disinfection efficacy of two different Er;Cr:YSGG laser units, with a 2790 nm wavelength, compared to ultrasonic-activated irrigation (UAI) in root canals infected with Enterococcus faecalis.
Methods: Human non-infected mandibular first molars were extracted, disinfected, and cultured with Enterococcus faecalis. Different types of Er;Cr:YSGG laser irrigation and UAI were performed according to the manufacturers\u27 protocols. The teeth were then processed for bacteriological and SEM analyses.
Results: The different laser-activated irrigation protocols showed multiple areas of remaining bacteria, biofilm, tissue, and thermal ablation. The laser fiber tips also displayed significant tip degradation after use, which might affect efficacy.
Conclusions: In this in vitro study, laser-activated irrigation using Er;Cr:YSGG technology and UAI were inefficient in eliminating pulp tissue from difficult-to-reach areas and Enterococcus faecalis from infected root canals
Human Salivary Gland Stem/Progenitor Cells for Tissue Engineering, SARS-CoV-2 Susceptibility, and Neurointegration
No full textSalivary glands and the saliva they secrete are important for digestion, chewing, and maintaining oral health. Reduced saliva production leads to a decreased quality of life for patients experiencing hyposalivation as a result of disease or injury, thus a large effort has been dedicated to developing materials and medium to recapitulate the structure of the gland for regenerative medicine. In doing so, we have come closer to developing a more complex model to study disease. These models, however, do not yet fully recapitulate the gland. In this dissertation, we describe a new cell source that can be used to develop tissue engineered salivary glands that are readily accessible through a minor incision of the lip. We then use these minor-gland derived salivary gland stem progenitor cells (hS/PCs) along with those isolated from major glands to understand salivary gland susceptibility to SARS-CoV-2, while also contributing data on mechanisms that might explain the ability of coronaviruses to infect salivary glands in the absence of its canonical receptor ACE2, which we conclusively showed is not present in salivary tissue or the basal cells of the ducts. Finally, we detail methods for co-culture of neural cells and salivary cells, including two different stem cell sources that can be differentiated into neural cells. This work also details methods used to create hyaluronic acid (HA) hydrogels that support the co-culture of hS/PCs and neural cells, with a focus on modifications to the hydrogels that allow forming neurites to traverse the material to form neural networks. Taken together, this work contributes new cell types and new methods for increasing the complexity of 3D tissue engineered salivary glands that can be used to better understand the normal functions and pathology of salivary glands
Joint Analysis of the nPOD-Virus Group Data: The Association of Enterovirus With Type 1 Diabetes Is Supported by Multiple Markers of Infection in Pancreas Tissue
No full textAims/hypothesis: Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated autoantibodies (AAbs), the latter representing preclinical disease. Two accompanying manuscripts from the nPOD-Virus Group report primary data from a coordinated analysis of multiple enterovirus indices. We aimed to comprehensively assess the association of multiple enterovirus markers with type 1 diabetes.
Methods: The nPOD-Virus Group examined pancreases from 197 donors, recovered between 2007 and 2019, classified into five groups: donors with type 1 diabetes, with residual insulin-containing islets (T1D-ICI group, n=41) or with only insulin-deficient islets (T1D-IDI, n=42); donors without diabetes who are AAb-negative (ND, n=83); and rare donors without diabetes expressing a single AAb (AAb+, n=22) or multiple AAbs (AAb++, n=9). We assessed the overall association of multiple indicators of enterovirus infection, case-by-case and between donor groups, as well as assay agreement and reproducibility, using various statistical methods. We examined data from 645 assays performed across 197 nPOD donors.
Results: Detection of enterovirus indices by independent laboratories had high reproducibility, using both enterovirus-targeted and unbiased methods. T1D-ICI donors had significantly higher (p\u3c 0.001) proportions of positive assay outcomes (58.4%) vs T1D-IDI (10.3%), ND (17.8%) and AAb-positive donors (AAb+ 24.6%; AAb++ 35.0%). Head-to-head comparisons revealed increased proportions of donors positive in two independent assays among T1D-ICI vs ND donors (VP1/HLA class I [HLA-I], p\u3c 0.0001; VP1/enterovirus-specific RT-PCR (EV-PCR), p=0.076; EV-PCR/HLA-I, p=0.016; proteomics/HLA-I, p\u3c 0.0001; VP1/proteomics, p=0.06). Among 110 donors examined for three markers (VP1, EV-PCR and HLA-I), 83.3% of T1D-ICI donors were positive in two or more assays vs 0% of ND (p\u3c 0.001), 26.7% of AAb+ (p=0.006), 28.6% of AAb++ (p=0.023) and 0% of T1D-IDI (p\u3c 0.001) donors.
Conclusions/interpretation: The nPOD-Virus Group conducted, to date, the largest and most comprehensive analysis of multiple indices of pancreatic enterovirus infections in type 1 diabetes; these were more prevalent in T1D-ICI and AAb++ donors than in other groups. Their preferential detection of these indices in donors with residual beta cells and autoimmunity implicates enterovirus infections across disease progression stages and supports a contribution to beta cell loss, directly or indirectly, even after diagnosis. The relatively small number of infected cells and the low amount of viral RNA support the existence of non-acute, low level, possibly persistent enterovirus infections in the pancreas
Survivorship From Pediatric and Adult Brain Tumors: The 2024 Brain Tumor Epidemiology Consortium Meeting Report
No full textThe Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology, including surveillance, classification, methodology, etiology, and factors associated with morbidity and survival. The 2024 annual BTEC meeting entitled “Survivorship from Pediatric and Adult Brain Tumors” was held in Mainz, Germany, USA, on May 15–17, 2024. The meeting gathered scientists from Africa, Australia, Europe, and North America and included 4 keynote sessions focusing on brain tumor survivorship across the age spectrum. The meeting included 3 abstract sessions, which also included scientific talks around brain tumor risk factors and predicting risk and survival. We also held a brainstorming session to form a near-term research strategy around brain tumor survivorship in the epidemiology community. This report provides a summary of the meeting content
Science Tikkun: A Bioscience Pandemic Framework in a Hebrew Tradition of Global Repair
No full textOver the past decade we have seen a steady increase in dangerous pandemic threats. They include two major Ebola epidemics and cholera in Africa; dengue, Zika, yellow fever in the Americas; a COVID-19 pandemic; and H5N1 in Texas. This is happening because of a confluence of modern forces including urbanization, deforestation, and climate change. Yet as pandemics emerge on a crowded and warming planet, anti-science disinformation and antisemitism impede our response. Science tikkun is an overarching framework for repair and redress. It honors the legacy of Maimonides, Teilhard de Chardin, and others who have sought reconciliation between science and religion
KinaseFusionDB: an integrative knowledge of kinase fusion proteins in multi-scales
Full text linkKinase fusion genes were the most targeted fusion gene group among multiple major cellular gene groups. Kinase inhibitors disrupt aberrant signaling cascades and inhibit tumor progression, yet the specific mechanisms of action of the U.S. Food and Drug Administration (FDA)-approved inhibitors in the context of kinase fusion oncoproteins remain largely unknown. This gap limits our ability to develop personalized therapies and next-generation kinase inhibitors. To address this, we developed a novel in silico pipeline for predicting 3D structures of kinase fusion proteins and performing structure-based virtual screening. This approach enables large-scale structural annotation and drug screening across pan-cancer kinase fusions. We present KinaseFusionDB, available at https://compbio.uth.edu/KinaseFusionDB, a comprehensive knowledgebase providing functional annotation of 7680 kinase fusion genes, 1399 predicted fusion protein structures, predicted Local Distance Difference Test (pLDDT)-based confidence scoring, and virtual screening data using FDA-approved kinase inhibitors. Our analysis revealed that most predicted structures showed high pLDDT scores (pLDDT \u3e70) within conserved kinase domains. Structural alignment with known Protein Data Banks demonstrated shared structural motifs despite variation in fusion breakpoints. Virtual screening results highlighted repurposing opportunities and isoform-specific binding preferences. KinaseFusionDB is a valuable resource for investigating kinase fusion structure-function relationships and guiding the design of personalized and next-generation kinase inhibitor therapies
Constructing A Conversation-First Dialogue Model for Comprehensive, Evidence-Based Counseling for HPV Vaccination for Young Adults
No full textThe human papillomavirus (HPV) vaccine has been shown to prevent several types of cancers; however, vaccination rates remain suboptimal. Effective patient-provider communication is key to promoting vaccination but is often hindered by various clinical barriers. Speech bots could be a promising solution by addressing common barriers and facilitating HPV vaccination uptake. We used a conversation first design approach to develop the interaction for speech bots to deliver HPV vaccination counseling to young adults. Two counseling strategies were developed and piloted: motivational interviewing (MI) and the theory-based approaches. Wizard of Oz experiments were conducted with young female adults (n = 24). Preliminary evidence shows that MI yielded higher usability than the theory-based approach. The theory-based approach significantly improved HPV vaccine beliefs and attitudes. These findings led to the development of a hybrid conversational model for future pilot testing and the eventual creation of a computable format for automated speech bots
Body Composition and Its Outcomes and Management in Multiple Sclerosis: Narrative Review
No full textBackground: There is emerging interest in obesity and its prevalence, outcomes, and management in people with multiple sclerosis (MS). Body mass index (BMI) is the traditional marker of obesity in MS, whereas body composition, inclusive of specific body tissue compartments (e.g., fat, bone, and muscle), is often overlooked despite its relevance.
Objective: This narrative review (a) underscored the use and utility of dual-energy X-ray absorptiometry (DEXA) as an accurate and reliable measure of body composition; (b) thematically analyzed and synthesized the current evidence regarding body composition (using DEXA); and (c) determined gaps to be addressed in future research. Methods: The structure and reporting of this narrative review followed the guiding criteria outlined in the Scale for the Assessment of Narrative Review Articles (SANRA). The relevant literature for this narrative review was identified via a PubMed search utilizing combined search terms such as ‘body composition’ and ‘multiple sclerosis’. The identified research was then organized by the authors into major themes and sub-themes. The articles described within the narrative review were based on saturation of the identified themes and sub-themes.
Results: Three major themes were identified, namely (1) comparison of body composition between people with MS and non-MS controls (2 meta-analyses); (2) examination of the relationships between body composition and a range of outcomes (14 cross-sectional studies); and (3) interventions that report and/or target body composition in MS (11 clinical trials).
Conclusions: This narrative review mapped the existing evidence regarding body composition in MS, and posits body composition as a novel, informative, and targeted concept for this population. The narrative review underscores the importance of randomized controlled trials that focus on body composition as a significant and modifiable outcome. Such research could improve the understanding of obesity and poor body composition in MS and identify useful clinical recommendations for diagnosis and management
Early Life Exposure To Fine Particulate Matter and Fine Motor Function, Attentional Function, and Working Memory Among Spanish School-Aged Children
No full textBackground: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.
Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had data from at least one neuropsychological assessment. General linear models were applied to assess associations between average prenatal and postnatal PM2.5 with each outcome. Distributed lag nonlinear models were used to explore refined periods of susceptibility to PM2.5. We reported β estimates and 99% credible intervals (CrI) representing the change in each outcome per 5-μg/m3 increase in PM2.5.
Results: Prenatal PM2.5 exposure was associated with decreased mean hit reaction time (HRT) (β = -21.82; 99% CrI = -64.1, 20.4) and HRT-standard error (β = -9.7; 99% CrI = -30.3, 10.9) on the ANT but estimates were imprecise. Postnatal PM2.5 was associated with reduced mean HRT on the n-back task (β = -39.4; 99% CrI = -115.1, 26.3). We observed sensitive periods of exposure in the postnatal period associated with both better and worse performance on the finger-tapping test and ANT.
Conclusions: We found limited evidence to support an association between PM2.5 exposure and fine motor function, attentional function, or working memory in school-aged children